BLOCK 3: IMM: (3.7) B-CELL ACTIVATION
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BLOCK 3: IMM: (3.7) B-CELL ACTIVATION

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Questions and Answers

What type of antigens lead to T-cell independent activation of B-cells?

  • Polysaccharide antigens
  • Thymus-independent antigens (correct)
  • Thymus-dependent antigens
  • Protein antigens
  • What characteristic do the epitopes of T-cell independent antigens typically have?

  • They are irregularly spaced on pathogen surfaces.
  • They are exclusively found in soluble forms.
  • They are complex and highly variable.
  • They occur in dense and regular arrays. (correct)
  • What role do follicular dendritic cells play in the B-cell area?

  • They store intact antigens and display them to B-cells. (correct)
  • They produce antibodies for B-cells.
  • They inhibit B-cell activation.
  • They activate T-cells directly.
  • What mechanism allows for the stimulation of B-cell proliferation and differentiation without T cells?

    <p>Clustering of BCRs and co-receptors at the B-cell surface</p> Signup and view all the answers

    In which B-cell population is T-cell independent activation predominantly seen?

    <p>B-1 cells</p> Signup and view all the answers

    What is a requirement for B cell activation?

    <p>Cross-linking of B-cell receptors</p> Signup and view all the answers

    Which component is part of the B-cell receptor complex?

    <p>Monomeric IgM</p> Signup and view all the answers

    What initiates a cascade of intracellular signals in B cells?

    <p>Cross-linking of B-cell receptors</p> Signup and view all the answers

    How does naïve B cell activation occur through a TFH?

    <p>Through cytokine release and BCR engagement with antigen</p> Signup and view all the answers

    What is the consequence of being unable to form germinal centers?

    <p>Reduced B cell differentiation</p> Signup and view all the answers

    What is the primary function of the B cell co-receptor?

    <p>To enhance the signaling of BCR upon antigen binding</p> Signup and view all the answers

    Where does somatic hypermutation and affinity maturation occur after B cell activation?

    <p>In germinal centers of lymph nodes</p> Signup and view all the answers

    What drives B cell activation, differentiation, and isotype switching?

    <p>The presence of specific cytokines</p> Signup and view all the answers

    What role does CR2 play in the B cell activation process?

    <p>It helps cross-link BCR and co-receptor for improved signaling.</p> Signup and view all the answers

    Which statement accurately describes the interaction between BCR and soluble antigens?

    <p>C3d tagging on soluble antigens enhances BCR cross-linking.</p> Signup and view all the answers

    What initiates the phosphorylation of the cytoplasmic tail of CD19?

    <p>Tyrosine kinases associated with BCR activation.</p> Signup and view all the answers

    Why do naive B cells require help from CD4 TFH cells?

    <p>To recognize pathogen-derived peptides through MHC class II.</p> Signup and view all the answers

    What is one consequence of BCR binding to antigen?

    <p>Internalization of the antigen through endocytosis.</p> Signup and view all the answers

    How does the structure of CR2 facilitate its function?

    <p>Its elongated and flexible structure allows cross-linking with diverse antigens.</p> Signup and view all the answers

    In what form does a naive B cell recognize an antigen?

    <p>By binding with its BCR.</p> Signup and view all the answers

    What is a key factor for B cell-mediated immunity during primary immune responses?

    <p>Conjugation with CD4 TFH cells.</p> Signup and view all the answers

    What role do follicular dendritic cells (FDCs) play in the recognition of antigens by naive B cells?

    <p>They capture antigens and present them to B cells.</p> Signup and view all the answers

    How are antigens with C3d brought to lymph nodes for B cell recognition?

    <p>By binding to CR2 on macrophages and FDCs.</p> Signup and view all the answers

    What process occurs after antigen activation of B cells in the lymph node?

    <p>B cells move towards the T-cell area.</p> Signup and view all the answers

    What is the specific interaction that stabilizes the synapse between TFH cells and B cells?

    <p>LFA-1 interactions with ICAM-1.</p> Signup and view all the answers

    What type of immunoglobulin do plasma cells primarily secrete upon activation?

    <p>IgM</p> Signup and view all the answers

    What role does CD40L play in the interaction between TFH cells and B cells?

    <p>It facilitates B cell survival signals.</p> Signup and view all the answers

    Which cellular structure is involved in the reorientation of the cytoskeleton during B-cell activation?

    <p>Microtubule-organizing center (MTOC)</p> Signup and view all the answers

    What is the primary location of clonal expansion for B cells in the lymph nodes?

    <p>Medullary cords</p> Signup and view all the answers

    What is the function of the cytoskeleton during the interaction between B cells and TFH cells?

    <p>It enables the formation of a stable synapse.</p> Signup and view all the answers

    What are the key molecules that are involved in the delivery of cytokines from TFH cells to B cells?

    <p>CD40L and soluble cytokines</p> Signup and view all the answers

    What is the primary location where B cells undergo affinity maturation and isotype switching?

    <p>Germinal center</p> Signup and view all the answers

    Which type of cell drives somatic hypermutation in centroblasts within the germinal center?

    <p>T follicular helper (TFH) cells</p> Signup and view all the answers

    What happens to centrocytes whose B cell receptors (BCRs) peak in affinity for antigen?

    <p>They express Bcl-xL and survive</p> Signup and view all the answers

    What is a major role of cytokines produced by TFH cells in the immune response?

    <p>To guide B cell switching of immunoglobulin isotypes</p> Signup and view all the answers

    Which of the following cells represent mature non-dividing B cells in the germinal center?

    <p>Centrocytes</p> Signup and view all the answers

    What is the consequence for centrocytes that experience mutations reducing their affinity for antigen?

    <p>They undergo apoptosis</p> Signup and view all the answers

    Which cytokine is recognized as the most potent inducer of terminal B-cell differentiation in humans?

    <p>IL-21</p> Signup and view all the answers

    In the germinal center, what are centroblasts primarily responsible for?

    <p>Rapidly dividing</p> Signup and view all the answers

    What role do follicular dendritic cells (FDCs) play in the germinal center?

    <p>They present antigens to centrocytes</p> Signup and view all the answers

    Which of the following is NOT a consequence of the interaction between centrocytes and TFH cells?

    <p>Inhibition of memory B cell formation</p> Signup and view all the answers

    Which part of the germinal center do centrocytes primarily occupy?

    <p>Light zone</p> Signup and view all the answers

    What is the fate of centrocytes that undergo successful affinity maturation?

    <p>They produce high-affinity antibodies</p> Signup and view all the answers

    Which process occurs within the germinal center as B cells undergo selection?

    <p>Affinity maturation</p> Signup and view all the answers

    What allows for the generation of diverse antibodies in B cells?

    <p>Somatic hypermutation</p> Signup and view all the answers

    The return of cognate pairs to the primary follicle primarily leads to the formation of what structure?

    <p>Germinal centers</p> Signup and view all the answers

    What is a key characteristic of self-reactive B cell receptors?

    <p>They lead to autoimmune conditions if not eliminated.</p> Signup and view all the answers

    At what stage do B cells exhibit increased specificity and affinity for antigens?

    <p>Upon repeated antigen exposure</p> Signup and view all the answers

    Which statement accurately describes the role of T cells in B cell activation?

    <p>T cells provide necessary signals for optimal B cell activation and proliferation.</p> Signup and view all the answers

    What occurs after the negative selection phase for B cells?

    <p>B cells enter positive selection.</p> Signup and view all the answers

    Why is affinity maturation important in B cell responses?

    <p>It ensures that B cells respond with higher affinity antibodies upon re-exposure to the same antigen.</p> Signup and view all the answers

    What happens to immature B cells that do not react to self antigens?

    <p>They continue in the developmental pathway and migrate to the bloodstream.</p> Signup and view all the answers

    What is the primary difference in negative selection between B cells and T cells?

    <p>B cells can undergo receptor editing if they react to self antigens.</p> Signup and view all the answers

    What is the result of positive selection for B cells during their development?

    <p>B cells that can bind directly to antigens are positively selected.</p> Signup and view all the answers

    Which of the following mechanisms allows B cells to modify their B cell receptors if they react to self antigens?

    <p>Receptor editing</p> Signup and view all the answers

    How do B cells that respond to self antigens compare to T cells in terms of selection?

    <p>B cells may undergo editing while T cells are only eliminated.</p> Signup and view all the answers

    In terms of B cell development, what characterizes immature B cells?

    <p>They can either develop further or be retained based on their interaction with self antigens.</p> Signup and view all the answers

    What is the fate of B cells that strongly react with self antigens during development?

    <p>They are retained in the bone marrow and may undergo receptor editing.</p> Signup and view all the answers

    What happens to B cells that bind to monovalent self-antigens during the selection process?

    <p>They become energetic and cannot respond to that antigen.</p> Signup and view all the answers

    Which statement best describes receptor editing in B cells?

    <p>Receptor editing allows B cells to modify their receptors to reduce self-reactivity.</p> Signup and view all the answers

    How does the process of T cell selection differ from B cell selection?

    <p>T cell selection focuses on affinity for peptide-major histocompatibility complexes, while B cell selection assesses direct antigen binding.</p> Signup and view all the answers

    What role does the lymphoid tissue play in the life cycle of mature B cells?

    <p>It facilitates the recirculation of mature B cells for antigen exploration.</p> Signup and view all the answers

    What is a characteristic feature of B cells before they leave the bone marrow?

    <p>They express only IgM and are negative for IgD.</p> Signup and view all the answers

    Study Notes

    B-cell Activation

    • B-cell activation requires cross-linking of the B-cell receptor (BCR).
    • The BCR complex consists of monomeric IgM bound to antigen, along with Igα and Igβ chains for intracellular signaling.
    • Multivalent antigens with regularly arrayed epitopes on pathogen surfaces can bind to IgM and cluster BCRs.
    • B-cell co-receptors, like CD19, synergize with BCR signaling.
    • Cross-linking of BCR and co-receptor increases the strength and efficiency of intracellular signaling.
    • Soluble antigens tagged with C3d can also activate B cells by cross-linking BCR and co-receptor.

    B-cell Activation with T-cell Help

    • Effective B-cell mediated immunity often requires help from CD4+ T follicular helper (TFH) cells.
    • Naive B cells internalize antigen, process it, and present it to T cells via MHC class II.
    • TFH cells recognize pathogen-derived peptides presented by MHC class II on B cells, leading to B cell activation.
    • TFH cells synthesize CD40 ligand (CD40L) which interacts with B-cell CD40 receptors.
    • TFH cells secrete cytokines like IL-21, which further contributes to B-cell activation.

    B-cell Independent Activation

    • T-cell independent activation of B cells (TI) occurs primarily in B-1 cells.
    • TI antigens typically have dense and regular arrays of epitopes on pathogen surfaces, leading to strong BCR clustering and activation.
    • TI activation does not require T-cell help, as the dense clustering of BCRs provides sufficient signaling.

    Follicular Dendritic Cells (FDCs)

    • FDCs in the B-cell area store intact antigens and display them to B cells.
    • FDCs act as antigen-presenting cells for B-cell activation.
    • FDCs express complement receptors (CR2) that bind antigens tagged with C3d.
    • This tethering of antigens to FDCs facilitates their presentation to naive B cells.

    B-cell Migration and Primary Focus

    • Antigen-activated B cells move to the T-cell area to find a TFH cell.
    • Activated B and TFH cells, forming a cognate pair, move to the medullary cords.
    • This area is known as the primary focus of B-cell expansion.
    • During this primary focus, B cells undergo clonal expansion and differentiation into IgM-secreting plasma cells.

    Germinal Centers and Secondary Focus

    • Some B cells from the primary focus return to the follicle, forming a germinal center.
    • The germinal center represents the secondary focus of B-cell expansion.
    • Germinal centers are sites where B cells undergo affinity maturation and isotype switching.

    Germinal Center Anatomy

    • Germinal centers are specialized microenvironments within the primary follicle.
    • They are composed of rapidly dividing B cells called centroblasts, which form the dark zone.
    • As centroblasts mature, they become non-dividing centrocytes, which form the light zone.
    • FDCs in the light zone present antigens to centrocytes.
    • TFH cells are present in the light zone and contribute to antigen-mediated selección of centrocytes.

    Affinity Maturation

    • Somatic hypermutation introduces mutations in the BCR genes of centroblasts.
    • Centrocytes with BCRs that exhibit increased affinity for the antigen survive, while those with decreased affinity undergo apoptosis.
    • This process drives affinity maturation of the B-cell response.

    Isotype Switching

    • TFH cells secrete cytokines that guide B-cell isotype switching.
    • IL-4 promotes switching to IgE.
    • IFN-γ promotes switching to IgG.
    • IL-5 promotes switching to IgA.
    • IL-10 and IL-21 promote both plasma cell and memory B cell differentiation.

    Plasma Cell and Memory B Cell Differentiation

    • TFH cells contribute to the differentiation of activated B cells into either plasma cells or memory B cells.
    • IL-10 and IL-21 drive the differentiation process.

    Ellen Vitetta

    • Ellen Vitetta is a prominent immunologist who made significant contributions to our understanding of B-cell biology.

    B cell negative selection

    • B cells are selected against if they react to self‐antigen, removing any cells that react to self‐antigen.
    • Cells that react to self-antigen are retained in the bone marrow, which contrasts with T cells where cells are killed directly.

    B cell positive selection

    • B cells are selected for if they can bind to antigen directly.
    • T cells are also positively selected, but this occurs based on their ability to recognize self molecules.
    • B cells go through negative selection before positive selection, whereas T cells go through positive selection before negative selection.
    • After positive selection, B cells that can bind to antigen are allowed to leave the bone marrow and circulate in the blood.

    B cell receptor editing

    • If a B cell reacts to self-antigen, the B cell receptor can be edited to change its specificity.

    B cell types

    • B2 cells are the most common type and they are active in the immune response.
    • B2 cells have a broad range of epitopes that they can recognize due to the rearrangement of their heavy and light chains during development.
    • B2 cells respond more quickly to repeated exposure to an antigen due to a process called affinity maturation.
    • Changes in immunoglobulin isotypes can happen due to a process called isotype switching.
    • B2 cells are responsible for the formation of memory B cells.

    Phases of development

    • The first phase of B cell development is defined by the process of receptor editing and focuses on selection processes.
    • The process of receptor editing happens before positive selection.
    • The second phase of development happens in secondary lymphoid tissues.
    • The third phase of development happens in the periphery.

    B cell maturation

    • Immature B cells express IgM and leave the bone marrow.
    • Mature B cells express both IgM and IgD.
    • B cells circulate in the blood and lymph.
    • They will re-enter secondary lymphoid tissues to initiate an immune response.

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